Taking a risk-based approach to product quality is an excellent way to uncover potential weaknesses in process designs or control strategies. A risk assessment is different from an impact assessment because the former considers the severity and the likelihood of the impact. A properly performed risk assessment is a valuable tool in designing experiments, defining design space, and planning design-of-control strategy. The ultimate goal of risk assessment is not only to achieve the desired quality, but also to produce predictable and consistent quality.

Target product quality and product-quality consistency

The target product quality in this instance may be the desired product quality for full-scale production or a quality that is sufficient for the current scale and stage of development. Product-quality variability is a common problem that can be difficult to solve. Product-quality risk assessment is an effective tool to reduce product-quality variability.

Quality impact assessment

The first stage of performing a risk assessment is identifying potential hazards. A hazard is something that influences the process directly or indirectly (e.g., materials of construction or instrumentation). A typical impact assessment will identify hazards, the type of hazards, and the documentation required such as material or calibration certificates.

Impact assessments are typically designed to identify potential hazards, but not the severity or frequency of exposure to the identified hazards. Since neither the severity nor the frequency of the hazards is identified, an impact assessment is inadequate for designing future experiments or control strategies.

Quality risk assessment

Risk is a combination of the severity of exposure to a hazard and the frequency of being exposed. Being struck by lighting is a good example of a low-risk hazard. Despite the severity of the hazard, the likelihood of it happening is small.

A product-quality risk assessment requires both product and process understanding to be performed effectively. Consequently, it is best performed after process development has been completed. Ideally, the target product quality is known at that point, including the extent to which the different product-quality attributes can vary without unacceptable quality loss. The limits of acceptable variability are rarely known for all product attributes, however. A quality risk assessment can often identify the aspects of the process that require further investigation. Quality risk assessment must be included in the experimental design or receive special attention in the control strategy.

It is important that personnel have adequate general understanding of the process type (in this case, spray drying), especially if the process will be scaled up at a later stage.

Applying control strategy

An ideal control strategy would allow large input variation but maintain low output variability. Unfortunately, these criteria are rarely met in the real world. A good control strategy would allow some input variation, maintain low output variability, and provide early warning of deviations. The success of such a control strategy is ultimately limited to known input variation. Process analytical technology (PAT) is a valuable tool in identifying input variation that previously was overlooked or deemed insignificant (because of multivariate effects, for example).

The control strategy can be simplified if the product-feed variations are small, as they frequently are. In this case, a good control strategy is to fix the process parameters that have the greatest product-quality impact by controlled variations in the process parameters with the least product-quality impact.

Spray drying

In a spray dryer, a liquid feed (e.g., solution, suspension, or emulsion) is atomized into a spray of fine droplets and suspended in gas while drying. Spray drying is a fast method of drying because of the product's large surface area and high heat-transfer coefficients. The product's large surface area also enables drying at low to moderate temperatures. The rapid drying and consequent fast stabilization at moderate temperatures make spray drying feasible for heat-sensitive materials.

Spray dryers must always be cleaned and sometimes sterilized. These and other subprocesses are often as critical as the main drying process, but are not part of the assessment as described below.